As shown in FIG. 1 an emulsion consists of droplets of one internal phase 10 dispersed in a second immiscible fluid 20, called an external or continuous phase. Examples of common emulsions are oil-in-water and water-in-oil emulsions. The conversion of the droplets to solidified particles has significant commercial applications. Existing ways to convert emulsion droplets to solidified particles include the introduction of chemical crosslinking agents that trigger chemical reaction crosslinking and polymerization upon stimuli, such as optical illumination and UV crosslinking. Other ways include heating, vacuum drying and freeze drying for a certain period of time. All of these ways require intensive external energy inputs and additional subsequent steps.
Osmosis-induced water extraction, i.e., osmotic dehydration, is now widely used in different fields, such as food preparations, agricultural formulations, red blood substitutes, cosmetics and pharmaceuticals. In the food industry, water is extracted from objects like fruits and vegetables by immersing them in an aqueous solution with a high osmotic pressure due to the high concentration of sugars and salts in the solution. Water in vegetable tissues can be partially removed using this method and thus preservation of food can be achieved. Control of the osmotic-pressure-driven water migration between the two aqueous phases in an emulsion system has also been reported.
When used in the food industry, the conversion of liquid flavor materials into easy-to-handle solids can improve the stability and can control the release of dried active food ingredients, such as flavors, enzymes, etc. Besides, it also provides protection against degrading reactions and prevents the loss of flavor.
Moreover, osmotic dehydration is used as a pre-treatment prior to freezing, freeze drying, vacuum drying and air drying. Control of the osmotic-pressure-driven water migration between the two aqueous phases in water/oil/water (W/O/W) emulsions has been reported and the dynamic of water transportation has also been studied. The process is affected by lots of parameters such as the magnitude of the osmotic pressure gradients between the two aqueous phases, the nature and concentrations of the surfactants, and the nature and viscosity of the oil phase, etc.
As disclosed in Kaymak-Ertekin, M. Sultanoglu, Journal of Food Engineering, 46, 243-250 (2000), osmosis-induced water extraction from raw material, such as fruits and vegetables, is achieved by placing the solid/semi solid material, whole or in pieces, in a hypertonic solution (sugar and/or salt) with a simultaneous counter diffusion of solutes from the osmotic solution into the tissues. The article recommends this processing method as a way to obtain better quality food products. Partial extraction of water allows structural, nutritional, sensory and other functional properties of the raw material to be modified.
Using a classical microfluidic device with an applied electrical field, the generation of droplets between two immiscible aqueous phases can be tuned and controlled. A method based on electrospray has been proposed to generate water-in-water (w/w) droplets in controlled size and uniformity. The method utilizes the electrical field applied to the microfluidic device to help control the formation of droplets. See, Z. Liu, H. C. Shum, Biomicrofluidics, 7, 044117 (2013).
Within all-aqueous emulsion systems, a method has been proposed to generate droplets of controlled and uniform diameter with a good production rate. The introduction of a perturbation through a mechanical vibrator has been suggested to produce droplets with controlled size and uniformity. The method suggests a biologically and environmentally friendly platform for droplet microfluidics and establishes the potential of water-in-water (w/w) droplet microfluidics for encapsulation-related applications. H. C. Shum, J. Varnell, D. A. Weitz, Biomicrofluidics, 6, 012808 (2012)
The phase diagrams at 22° C. for aqueous two-phase systems composed of dextran and polyethylene glycol (PEG) solutions are determined in the article, A. D. Diamond, J. T. Hsu, Biotechnology Techniques, 3, 119-124 (1989). The effects of the molecular weight of PEG and dextran on phase separation are illustrated in the article.
Recent advances in the generation of particles based on emulsion systems have led to applications in various fields such as the food, cosmetics and drug delivery industries. When the preservation of the bioactivity of particles in the form of encapsulated delicate components is desired, the fabrication conditions as well as the process should be biocompatible. All-aqueous emulsions can be generated using the so-called aqueous two-phase systems (ATPS), which form two immiscible aqueous phases with attractive features, such as their biocompatibility or their non-toxicity. Thus, in the medical industry, micro-particles can be used as safe carriers for controlling the release of bioactive compounds.
Micro-particles made from all-aqueous emulsions have the potential to become one of the most promising and extensively used mediums for encapsulation due to their non-toxicity, storage stability, cost-effectiveness as well as the simplicity of the fabrication process. They can be fabricated by different kinds of methods, such as a spray drying method or a traditional homogenization methods. The latter one needs an additional step to solidify the emulsion droplets; one common way to do so is to introduce chemical crosslinking agents that trigger crosslinking and/or polymerization upon stimuli, including optical illumination. So far, there have been no reports concerning the osmotic drying of micro-particles in all-aqueous emulsion systems without further external energy or chemical inputs.
Micro-particles, like starch, gelatin and dextran micro-particles, can be prepared by traditional homogenization crosslinking methods using additional chemicals as crosslinking agents. For example, in a previous study cross-linked gelatin microspheres with encapsulated bone morphogenetic protein 2 were fabricated by an emulsification process and stabilized by crosslinking with a small molecule with genipin as the crosslinking agent. To get the final solidified particles or microspheres after crosslinking, the microspheres need to be further incubated at −80° C. for 2 hours before being lyophilized. The whole process requires intensive external energy inputs and can be very time-consuming. See, L. Solorio, C. Zwolinski, A. W. Lund, M. J. Farrell, and J. P. Stegemann, Journal of Tissue Engineering and Regenerative Medicine, 4, 514-523 (2010)
Other emulsion-based methods always require additional steps, such as external agitation, heating, vacuum drying or freeze drying, for certain duration of time before fully dried micro-particles can be obtained. Moreover, these methods are all highly energy-intensive. In addition, other active ingredients, such as biological cells, tissues, drugs, DNA and leading compounds including proteins, for encapsulation in micro-particles require delicate handling for proper protection of their bioactivities and good preservation of their inherent properties
Accordingly, it is desired to provide a generic method for one-step fabrication of solidified particles based on an all-aqueous emulsion containing two immiscible aqueous phases.